Cytokine storm: How COVID-19 patients' immune systems may fatally turn on them

TORONTO --
While some COVID-19 patients experience mild symptoms and recover on their own at home, others appear to be healthy one minute and in hospital fighting for their lives the next.

This rapid deterioration, along with other clinical signs, have led some researchers to believe that certain patients’ immune systems are betraying them by overreacting to the virus.

The phenomenon is broadly known as a “cytokine storm” and it has been well-documented since long before the world became aware of the new coronavirus. In fact, there are some scientists who believe cytokine storms may explain why otherwise healthy young people died from the Spanish flu in 1918.

According to Dr. Douglas Fraser, a lead researcher and pediatric critical care physician at London Health Sciences Centre in Ontario, a cytokine storm can occur when the immune system initiates an “exaggerated” response to an infection.

During an immune response, the body produces cytokines, which are molecules that are released by certain cells into the bloodstream to help co-ordinate an attack against the infection. Ordinarily, the body fights produces enough cytokines to fight off the virus or bacterium and then stops once the invader has been defeated.

In a cytokine storm, the immune system goes into overdrive and continues to release the molecules, which then end up attacking the very organs they were intended to protect.

If left untreated, the effects of this overreaction by the immune system can lead to fatal outcomes from complications such as multi-organ failure, lung inflammation, bacterial pneumonia, and respiratory distress.

In the current pandemic, Fraser said the research on how cytokine storms may affect COVID-19 patients is still very much in its infancy. However, recent studies out of China and Europe appear to provide evidence of elevated levels of cytokines and other immune molecules characteristic of a cytokine storm in COVID-19 patients.

Fraser said physicians have observed in their patients high fevers, elevated levels of the protein ferritin, which occurs during inflammation, and multiple cell lines with low levels of hemoglobin, white blood cells and/or platelets.

“All of these things can occur from elevated cytokines,” he explained. “So there's no evidence, no convincing evidence yet to show that a cytokine storm is occurring; however, it’s been suggested, based on these clinical symptoms.”

TREATMENT FOR THE STORM

While there is some speculation that cytokine storms may explain why younger, otherwise healthy, individuals have died from COVID-19, Fraser said it’s still too early to know if that’s the case.

“It could be from a whole variety of factors, everything from genetics to pre-existing conditions, maybe people just don't know about yet, or, or haven't been discovered yet,” he said. “We just don’t know why certain people are getting sick and why certain people are not.”

Fraser said there could be a number of reasons why some individuals become deathly ill from the disease and others don’t. In order to understand these different outcomes, he said researchers have to investigate the cytokines and other molecules present in COVID-19 patients.

“The goal is to determine what exactly is happening with the immune system and the inflammation it’s causing,” he said.

To achieve this, Fraser and a team of researchers from Lawson Health Research Institute and Western University have been collecting daily blood samples from presumed COVID-19 patients over the past two weeks to test for inflammatory biomarkers and monitor how they change over time.

The information is then compared to that of other patients with infections unrelated to COVID-19.

“We’re comparing those samples to see what molecules have changed,” he said. “The important aspect there is that we identify which cytokines and molecules are different, then we can start to develop therapies that are specific against them.”

There are already some treatments that have been used to help reduce cytokine storms in the past, but it’s still not clear how effective they would be in COVID-19 patients.

Some of those therapies include the use of steroids, intravenous immunoglobulin or donated blood containing healthy antibodies, and drugs used to suppress cytokines, such as tocilizumab and anakinra.

The problem with these treatments, according to Fraser, is they’re not necessarily patient-specific, which is important when dealing with the individual complexities of immune responses.

“It all depends on what cytokines are released, because there’s a whole family of them, and it also depends on where they're released and from what cell,” he explained.

That’s why Fraser said he’s hopeful the results of his study will provide some insight into how the immune system reacts to COVID-19 and which specific therapies should be used to treat certain patients.